The Immunopathology Core will continue to provide support to the Program in the same areas that it has done during the previous period. These include primarily the characterization in tissues of new anti-CEA monoclonal antibodies (MAbs) and constructs that Project 0002 will generate. their immunoreactivities will be tested using immunohistochemical methods (IHC) in hundreds of colorectal carcinomas and normal tissues to establish their sensitivity and specificity. In the clinical imaging trials, all the tissues removed at surgery will be evaluated by microscopic and immunohistochemical techniques to correlate histologic/phenotypic parameters with antibody uptake in the neoplastic and normal tissues. In the pre-clinical and clinical therapy trials (Project 0005) we will continue to evaluate the toxic effects that RIT with the various preparations has in normal organs by comprehensively studying with light, and when needed, electron microscopic methods every organ at different times post-treatment. Likewise, we will support and interact with other investigators, specifically in Project 0006 and Cores 9004 and 9006, in their needs to analyze the cellular/histologic, phenotypic, DNA and cell cycle, etc. changes occurring after radioimmunotherapy (RIT) alone or combined with other therapeutic modalities. Two additional aims have been kept in the current application: a) to explore other human malignant neoplasias (lung and breast) that express significant amount of CEA; and b) to improve and combine immunohistochemical and autoradiographic techniques that will allow in situ quantitation of the radiolabelled MAbs (RMAbs). The former aim is directed to increment the spectrum of cancers that could benefit from RIT with anti-CEA MAbs. The latter aim will also support studies carried out in Project 0006 and Core 9004. Specifically, this methodology will allow to correlate various histologic, phenotypic and cell cycle parameters with the RMAb uptake. Similarly, quantification of the radioactivity in tissue sections of the tumor and normal organs will be performed leading to accurate dosimetric estimations.